Italian Real-Life Experience of Patients with Hereditary Transthyretin Amyloidosis Treated with Patisiran.

Hereditary transthyretin amyloidosis (ATTRv) is a multisystemic, rare, inherited, progressive and adult-onset disease, affecting the sensorimotor nerves, heart, autonomic function and other organs. The actual scenario of pharmaceutical approaches for ATTRv amyloidosis includes five main groups: TTR stabilizers, TTR mRNA silencers, TTR fibril disruptors, inhibitor of TTR fibril seeding and gene therapy. Patisiran is a small, double-stranded interfering RNA encapsulated in a lipid nanoparticle, able to penetrate into hepatocytes, where it selectively targets TTR mRNA, reducing TTR production. We report and discuss 9 cases of different patients with ATTRv amyloidosis successfully managed with patisiran in the real clinical practice. Literature data, as well as the above presented case reports, show that this drug is effective and safe in improving both neurological and cardiovascular symptoms of ATTRv amyloidosis, and to maintain a good QoL, independently form the stage of the disease and the involved mutation. Recent studies correlated improved functional and biochemical outcomes with a regression of amyloid burden, especially at the cardiac level. Today, patisiran can be considered a valid therapeutic option for the management of patients with ATTRv amyloidosis and polyneuropathy and cardiovascular symptoms.
Competing Interests: Fanara S, Fava A, Ferrero B, Gentile L, Giorgi M, Perfetto F, Poli L, Russo M, Russo D, Vastola M declare no conflicts of interest in this work. Di Stefano V received congress and travel accommodation expense compensations from Alnylam. Guaraldi P has been advisory board member of Alnylam; received speaker fees and honoraria from Theravance Biopharma, Akcea Therapeutics and Chiesi; received congress and travel accommodation expense compensations from Alnylam, Bial, Zambon, AbbVie and Sobi, non-financial support from Pfizer. Leonardi L received travel grants from Swedish Orphan Biovitrum AB (SOBI) and speech/board grants from Alnylam Pharmaceutical. Tagliapietra M received travel grants from Alnylam and Sobi and a training grant sponsored by Pfizer.
(© 2022 Di Stefano et al.)